Antiseptic sclerosing agents



Patented Aug. 17, 1937 UNITED STATES ANTISEPTIC SOLEROSING AGENTS Edmond E. Moore, Waukegan, Ill., assignor to Abbott Laboratories, North Chicago, 111., a corporation of Illinois No Drawing. Application October 29, 1934, Serial No. 750,597

9 Claims.

My invention relates to compositions of matter which are especially valuable therapeutically in the sclerosing of varicose veins by injection thereinto. My improved products are advantageous as compared with materials which have been heretofore suggested for the same purpose, in that my products are of low toxicity, are antiseptic, stable, of constant composition, and form clear and transparent solutions.

Aqueous solutions of certain soaps have heretofore been suggested in this connection but have not been entirely satisfactory for the reasons that they have been unstable, of variable composition, and lacking in antiseptic properties. 15 I have found that amine soaps of fatty acids are superior in many respects as sclerosing agents to any of the previously suggested sclerotic materials. I have prepared and tested fatty acid soaps of mono-, di-, and tri-alkyl amines and also of aryl amines, and solutions of said soaps have, on test, shown markedly lower toxicities than any of the soaps heretofore suggested in this connection. Such soaps embodying my invention, in addition to low toxicity, are stable in solution for long periods and have various other advantages. It has been found, after extensive investigation, that in the treatment of varicose veins by the injection method the antisepsis of solutions is an extremely important matter. (See Kilbourne, The American Journal of Surgery, July 1934, pages 148-154). High stability of solutions which are used for the sclerosing of varicose veins is thus desirable. The compounds embodying my invention have this feature.

Attempts have been made in the past, furthermore, to combine soaps which were heretofore suggested in this connection with organic bactericidal agents, in view of the great danger of infecting a patient incidental to the injection. Such attempts have been quite unsuccessful for the reason that the bactericide was decomposed or thrown out of solution. A highly important feature of my invention is that the soaps which I have found to be of improved sclerotic value may be mixed in solution with highly efficient organic bactericidal and bacteriostatic agents to form valuable new compositions for the treatment of varicose veins. Such mixtures are very stable and will not react with each other or otherwise deteriorate over long periods of time.

Improved compounds constituting my invention may be produced by combining an acidic antiseptic material with an amine of the general type /RII RN Where R is a hydroxy-aliphatic or aromatic-hydroxy-aliphatic group, R" is hydrogen, an al kyl, an aryl, or a hydroxy-alkyl group and R is hydrogen, or a hydroxy-alkyl group, and a fatty acid to form a soap.

General method The amine and the antiseptic are mixed until a clear solution results. In certain cases, an excess of amine over that required to unite with the antiseptic and the fatty acid is necessary, in order to secure a transparent solution in water. Solvents, such as water, alcohol, etc., are required to give complete reaction between the amine and the antiseptic in some cases. The fatty acid is then added and the mixture is stirred. It is not necessary that the reaction between the amine and the fatty acid be complete before the addition of water. This mixture is then added to the required amount of warm water, stirred, and filtered. The above step sequence may be changed; for example, if an excess of amine over that required to combine with the fatty acid is used, the antiseptic may be added last, i. e., to the aqueous soap solution.

Example 10.0 grams of monoethanolamine are added to 0.2 gram of 4-nitro-anhydro-hydroxy-mercuriortho cresol. The mixture is stirred until a clear solution results. 40 grams of oleic acid are then added and the mixture is again stirred. The resulting soap is added to 950 cc. of warm water and stirred until dissolved. A clear brilliant solution results. Alcohols may be added without influencing the stability. Such solutions show no indication of change after six months or longer. The following preparations are made similarly:

Where R is one of the group consisting of hydroxy-aliphatic and aromatic hydroXy-aliphatic,

- Fatty Soap Antiseptic Amine acid cum Antiseptic (mum Percent Percent M o n o e t h a n 1- Oleic 4-nitro anhydro hydroxy- 0.02

amine. mercuri ortho cresol. o do 0. 04 Dodo 5 0.10 Do. do 0.02 Do. Laurie. 5 0.02 Do Erucic 5 do 0.02 5 Ethy mercuri thiosalicylic 0.02

am 5 Oxymercuri ortho-nitro- 0.02

phenol. 5 2:7 dibrom 4-hydroxy mer- 0. 02

curi fluorescein 5 0.5 5 0. 4 5 0.02 5 Methyl ester of pa 0. 1

droxy benzoic acid. I 5 Ethyl ester of para hydroxy 0.05

benzoic acid. 5 Propyl ester of para hydrcxy 0. 05

benzoic acid. Diethanolamine... do 5 4-nitro anhydro hydroxy 0.02

mercuri ortho cresol. Triethanolamine. do 5 --do 0.02 Triethanolamine do 5 .do 0.02

crude. Ephedrine do 5 do 0. 02 Pseudoephedrine. d0 5 0.02 Phenyl ethanoldo. 5 0.02

amine.

Various modifications of my invention will doubtless suggest themselves to those skilled in the art Without departing from the spirit of my invention. Hence, I do not Wish to be restricted to the specific embodiments or details disclosed above except to the extent indicated by the appended claims, which are to be interpreted as broadly as the state of the art will permit.

I claim as my invention:

1. A sclerosing agent comprising an aqueous solution of a soap formed of an amine having the type formula where R is one of the group consisting of hydroxy-aliphatic and aromatic hydroxy-aliphatic, R is one of the group consisting of hydrogen, alkyl, aryl and hydroXy-alkyl, and R is one of the group consisting of hydrogen, and hydroxyalkyLan-d a higher fatty acid.

2. A solerosing agent comp-rising an aqueous solution of a minor proportion of an acidic antiseptic material in combination With an amine of the general formula R. is one of the group consisting of hydrogen,

alkyl, aryl and hydroxy-alkyl and R is one of the group consisting of hydrogen, and hydroxyalkyl, together with a soap formedof a higher fatty acid and an amine of the same general formula.

3. A sclerosing agent comprising an aqueous solution of a soap formed of a higher fatty acid and an ethanolamine.

4. A sclerosing agent comprising an aqueous solution of a soap formed of oleic acid and monoethanolamine.

5. A sclerosing agent comprising an aqueous solution of a soap formed of lauric acid and an ethanolamine.

6. A sclerosing agent comprising an aqueous solution of a soap formed of erucic acid and an ethanolamine.

'7. The sclerosing solution described in claim 3 containing the reaction product of an acidic antiseptic material and an ethanolamine.

8. The sclerosing solution described in claim 4 containing the reaction product of a phenolic antiseptic material and an ethanolamine.

9. A sclerosing agent comprising an aqueous solution of a soap formed of oleic acid and mono-.

ethanolamine and the reaction product of 4- nitro-anhydro-hydroxy-mercuri-ortho-cresol and monoethanolamine.

EDMOND E. MOORE. 

